The gut microbiota (GM) plays an important role in modulating the effectiveness and toxicity of chemotherapy (CT) in children with oncological diseases. In this review, the authors analyzed and systematized current data on the role of GM in the tolerability and effectiveness of therapy in acute leukemias and demonstrated the interrelation between CT and GM. Chemotherapy causes changes in GM: it reduces the number of different bacterial species, decreases the number of beneficial species, and increases the abundance of opportunistic bacteria, which increases the risk of complications such as mucositis, febrile neutropenia, and sepsis. The reciprocal effect of GM on CT occurs through direct impact on the metabolism of cytostatics and systemic immunomodulation. One of the important mechanisms of GM influence is the formation of short-chain fatty acids, particularly butyrate, which enhances the function of cytotoxic T-lymphocytes, induces apoptosis of tumor cells, and supports normal intestinal function. Promising directions for dysbiosis correction are probiotics, prebiotics, and fecal microbiota transplantation, which shows high effectiveness in steroid-resistant graft-versus-host disease. Integration of microbiome biomarker research into prognostic models and the use of multi-omics technologies provide an opportunity for the development of individualized treatment approaches. Based on the available data, GM is an important factor in the effective delivery of CT in children, and methods of its modification have high potential for improving survival and quality of life in these patients, which requires further confirmation in randomized controlled trials.